Biomarkers of inflammation in major vascular surgery: a prospective randomised trial

Lindholm, Espen; Aune, Erlend; Seljeflot, Ingebjørg; Otterstad, Jan Erik; Kirkebøen, Knut Arvid

doi:10.1111/aas.12466

Cited by 18 publications

(19 citation statements)

References 67 publications

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“…We also introduced a unique control group consisting of patients without sepsis or AKI who match the septic patients by age, gender, comorbidities and a type of surgery. The previous studies on MMP-9 and TIMP-1 levels in sepsis compared septic patients to either healthy individuals (Lauhio et al 2011;Muhl et al 2011;Yazdan-Ashoori et al 2011;Wang et al 2014) or other critically ill patients or they compared different subgroups of septic patients (Lorente et al 2014) not taking into account any possible effects of surgery-induced inflammation (Helmersson-Karlqvist et al 2012;Lindholm et al 2015) or comorbidities on MMP-9 and TIMP-1 levels. Comorbidities present in patients with sepsis could alter levels of MMP-9 and TIMP-1 (Vandooren et al 2013;Galliera et al 2015) and are also considered as independent risk factors for AKI in the perioperative period (Kheterpal et al 2009).…”

Section: Discussionmentioning

confidence: 99%

“…The activity of the MMP-9 is closely regulated on multiple levels including the inhibition by regulatory proteins, such as tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) (Galliera et al 2015). Surgery-induced inflammation (Helmersson-Karlqvist et al 2012;Lindholm et al 2015) and sepsis (Muhl et al 2011;Lauhio et al 2011;Yazdan-Ashoori et al 2011;Lorente et al 2014;Wang et al 2014) are associated with altered levels of MMP-9 and TIMP-1. Increased MMP-9 and TIMP-1 expression has also been reported in a variety of AKI animal model studies (Maitra et al 2010;Teng et al 2012) but only one clinical study evaluated MMP-9 as diagnostic biomarker of AKI and not SA-AKI per se (Han et al 2008).…”

Section: Introductionmentioning

confidence: 99%

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Diagnostic Value of Matrix Metalloproteinase-9 and Tissue Inhibitor of Matrix Metalloproteinase-1 in Sepsis-Associated Acute Kidney Injury

Bojić

Kotur‐Stevuljević

Kalezić

et al. 2015

Tohoku J. Exp. Med.

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Sepsis-associated acute kidney injury (SA-AKI) severely impacts morbidity and mortality in surgical patients with sepsis. Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) have an important role in pathophysiology of sepsis but they have been unexplored in SA-AKI. We aimed to investigate the role of MMP-9 and TIMP-1 in septic surgical patients with SA-AKI and to evaluate them as diagnostic biomarkers of SA-AKI. This prospective observational study compared 53 major abdominal surgery patients with sepsis divided into SA-AKI (n = 37) and non-SA-AKI (n =16) group to 50 controls without sepsis matched by age, gender, comorbidities and type of surgery. Blood and urine samples from septic patients were collected on admission to ICU and 24, 48, 72 and 96 h later and once from the controls. The levels of MMP-9, TIMP-1, neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1, urea and creatinine were measured. MMP-9/TIMP-1 ratio and disease severity scores, such as Sequential Organ Failure Assessment (SOFA), were calculated. Septic patients with SA-AKI had higher serum TIMP-1 levels and lower serum MMP-9 levels and lower MMP-9/TIMP ratio, compared to septic patients without SA-AKI and controls. The levels of these biomarkers did not change significantly over time. MMP-9, TIMP-1 and MMP-9/TIMP-1 ratio correlated with urea, creatinine, NGAL, and SOFA scores. Moreover, using the area under ROC curve, we showed that TIMP-1 and MMP-9/TIMP-1 ratio, but not MMP-9, were good diagnostic biomarkers of SA-AKI. We report for the first time the potential diagnostic value of TIMP-1 and MMP-9/TIMP-1 ratio in SA-AKI.Keywords: acute kidney injury; biomarker; matrix metalloproteinase-9; sepsis; tissue inhibitor of matrix metalloproteinase-1 Tohoku

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Diagnostic Value of Matrix Metalloproteinase-9 and Tissue Inhibitor of Matrix Metalloproteinase-1 in Sepsis-Associated Acute Kidney Injury

Bojić

Kotur‐Stevuljević

Kalezić

et al. 2015

Tohoku J. Exp. Med.

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“…Little is known about the post-hospital survival for critically ill vascular surgery patients in general or the specific risk factors for adverse outcomes in this population. The existing studies on risk factors and predictive models of outcomes following vascular surgery are not focused on those requiring critical care [4–7]. …”

Section: Introductionmentioning

confidence: 99%

Red cell distribution width at hospital discharge and out-of hospital outcomes in critically ill non-cardiac vascular surgery patients

Meijenfeldt¹,

Laan²,

Zeebregts³

et al. 2018

PLoS ONE

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ObjectiveRed cell distribution width (RDW) is associated with mortality and bloodstream infection risk in the critically ill. In vascular surgery patients surviving critical care it is not known if RDW can predict subsequent risk of all-cause mortality following hospital discharge. We hypothesized that an increase in RDW at hospital discharge in vascular surgery patients who received critical care would be associated with increased mortality following hospital discharge.Design, setting, and participantsWe performed a two-center observational cohort study of critically ill non-cardiac vascular surgery patients surviving admission 18 years or older treated between November, 1997, and December 2012 in Boston, Massachusetts.ExposuresRDW measured within 24 hours of hospital discharge and categorized a priori as ≤13.3%, 13.3–14.0%, 14.0–14.7%, 14.7–15.8%, >15.8%.Main outcomes and measuresThe primary outcome was all cause mortality in the 90 days following hospital discharge.ResultsThe cohort included 4,715 patients (male 58%; white 83%; mean age 62.9 years). 90 and 365-day post discharge mortality was 7.5% and 14.4% respectively. In the cohort, 47.3% were discharged to a care facility and 14.8% of patients were readmitted within 30 days. After adjustment for age, gender, race, Deyo-Charlson comorbidity Index, patient type, acute organ failures, prior vascular surgery and vascular surgery category, patients with a discharge RDW 14.7–15.8% or >15.8% have an adjusted OR of 90-day post discharge mortality of 2.52 (95%CI, 1.29–4.90; P = 0.007) or 5.13 (95%CI, 2.70–9.75; P <0.001) relative to patients with a discharge RDW ≤13.3%. The adjusted odds of 30-day readmission in the RDW >15.8% group was 1.52 (95%CI, 1.12–2.07; P = 0.007) relative to patients with a discharge RDW ≤13.3%. Similar adjusted discharge RDW-outcome associations are present at 365 days following hospital discharge and for discharge to a care facility.ConclusionsIn critically ill vascular surgery patients who survive hospitalization, an elevated RDW at hospital discharge is a strong predictor of subsequent mortality, hospital readmission and placement in a care facility. Patients with elevated RDW are at high risk for adverse out of hospital outcomes and may benefit from closer post discharge follow-up and higher intensity rehabilitation.

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“…In preclinical studies, MCP-1 expression was upregulated immediately after ischemia reperfusion injury(10) and MCP-1 inhibition was associated with lower cardiac fibrosis(11). In small human studies, MCP-1 expression increased immediately after cardiac surgery(12,13) and MCP-1 elevation was associated with AKI(14). Moreover, studies have used MCP-1 as a surrogate marker to quantify intra-operative inflammation after various interventions(13,15).…”

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confidence: 99%

“…In small human studies, MCP-1 expression increased immediately after cardiac surgery(12,13) and MCP-1 elevation was associated with AKI(14). Moreover, studies have used MCP-1 as a surrogate marker to quantify intra-operative inflammation after various interventions(13,15). However, the association of MCP-1 with post-cardiac surgery outcomes has not been examined in a large, prospective cohort.…”

mentioning

confidence: 99%

Plasma Monocyte Chemotactic Protein-1 Is Associated With Acute Kidney Injury and Death After Cardiac Operations

Moledina

Isguven

McArthur

et al. 2017

The Annals of Thoracic Surgery

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Background Monocyte chemotactic protein-1 [MCP-1; chemokine C-C Ligand-2 (CCL-2)] is upregulated in ischemia-reperfusion injury and is a promising biomarker of inflammation in cardiac surgery. Methods We measured pre- and postoperative plasma MCP-1 levels in adult patients undergoing cardiac surgery to evaluate the association of perioperative MCP-1 levels with acute kidney injury (AKI) and mortality in TRIBE-AKI- a prospective, multicenter, observational cohort. Results Of the 972 participants in the study, 329 (34%) developed AKI and 45 (5%) developed severe AKI. During median follow-up of 2.9 (2.2–3.5) years, 119 (12%) participants died. MCP-1 levels were significantly higher in those who developed AKI and mortality as compared to those without AKI and mortality, respectively. Participants with preoperative MCP-1 level in the highest tertile (>196 pg/ml) had an increased AKI risk as compared to those in the lowest tertile [<147 pg/ml; OR, 1.43 (1.00–2.05)]; the association appeared similar but was not significant for the severe AKI outcome [OR, 1.48 (0.62–3.54)]. As compared with participants with preoperative MCP-1 level in the lowest tertile, those in the highest tertile had higher adjusted mortality risk [HR, 1.82 (1.40–2.38)]. Similarly, as compared to participants with postoperative MCP-1 level in the lowest tertile, those in the highest tertile had higher adjusted mortality risk [HR, 1.95 (1.09–3.49)]. Conclusions Higher plasma MCP-1 is associated with increased AKI and mortality risk after cardiac surgery. MCP-1 could be used as a biomarker to identify high-risk patients for potential AKI prevention strategies in the setting of cardiac surgery.

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Biomarkers of inflammation in major vascular surgery: a prospective randomised trial

Abstract: We found an inflammatory response during the observation period, which was modified by the anaesthetic regimen in the early phase. This short-lasting difference is probably too short to support a cardioprotective effect of sevoflurane compared with TIVA in open abdominal aortic surgery.

Cited by 18 publications

References 67 publications

Diagnostic Value of Matrix Metalloproteinase-9 and Tissue Inhibitor of Matrix Metalloproteinase-1 in Sepsis-Associated Acute Kidney Injury

Diagnostic Value of Matrix Metalloproteinase-9 and Tissue Inhibitor of Matrix Metalloproteinase-1 in Sepsis-Associated Acute Kidney Injury

Red cell distribution width at hospital discharge and out-of hospital outcomes in critically ill non-cardiac vascular surgery patients

Plasma Monocyte Chemotactic Protein-1 Is Associated With Acute Kidney Injury and Death After Cardiac Operations

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